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2. Roadmap for alleviating the manifestations of ageing in the cardiovascular system

Author

Liberale, Luca, Tual-Chalot, Simon, Sedej, Simon, Ministrini, Stefano, Georgiopoulos, Georgios, Grunewald, Myriam, Bäck, Magnus, Bochaton-Piallat, Marie-Luce, Boon, Reinier A., Ramos, Gustavo Campos, de Winther, Menno P. J., Drosatos, Konstantinos, Evans, Paul C., Ferguson, Jane F., Forslund-Startceva, Sofia K., Goettsch, Claudia, Giacca, Mauro, Haendeler, Judith, Kallikourdis, Marinos, Ketelhuth, Daniel F. J., Koenen, Rory R., Lacolley, Patrick, Lutgens, Esther, Maffia, Pasquale, Miwa, Satomi, Monaco, Claudia, Montecucco, Fabrizio, Norata, Giuseppe Danilo, Osto, Elena, Richardson, Gavin D., Riksen, Niels P., Soehnlein, Oliver, Spyridopoulos, Ioakim, Van Linthout, Sophie, Vilahur, Gemma, Wentzel, Jolanda J., Andrés, Vicente, Badimon, Lina, Benetos, Athanase, Binder, Christoph J., Brandes, Ralf P., Crea, Filippo, Furman, David, Gorbunova, Vera, Guzik, Tomasz J., Hill, Joseph A., Lüscher, Thomas F., Mittelbrunn, María, Nencioni, Alessio, Netea, Mihai G., Passos, João F., Stamatelopoulos, Kimon S., Tavernarakis, Nektarios, Ungvari, Zoltan, Wu, Joseph C., Kirkland, James L., Camici, Giovanni G., Dimmeler, Stefanie, Kroemer, Guido, Abdellatif, Mahmoud, and Stellos, Konstantinos

Published
2025
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3. Targeting cIAP2 in a novel senolytic strategy prevents glioblastoma recurrence after radiotherapy

Author

Tomimatsu, Nozomi, Di Cristofaro, Luis Fernando Macedo, Kanji, Suman, Samentar, Lorena, Jordan, Benjamin Russell, Kittler, Ralf, Habib, Amyn A, Espindola-Netto, Jair Machado, Tchkonia, Tamara, Kirkland, James L, Burns, Terry C, Sarkaria, Jann N, Gilbert, Andrea, Floyd, John R, Hromas, Robert, Zhao, Weixing, Zhou, Daohong, Sung, Patrick, Mukherjee, Bipasha, and Burma, Sandeep

Published
2025
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6. Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes

Author

Hambright, William S, Duke, Victoria R, Goff, Adam D, Goff, Alex W, Minas, Lucas T, Kloser, Heidi, Gao, Xueqin, Huard, Charles, Guo, Ping, Lu, Aiping, Mitchell, John, Mullen, Michael, Su, Charles, Tchkonia, Tamara, Netto, Jair M Espindola, Robbins, Paul D, Niedernhofer, Laura J, Kirkland, James L, Bahney, Chelsea S, Philippon, Marc, and Huard, Johnny

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Arthritis, Clinical Research, Aging, Prevention, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Inflammatory and immune system, Musculoskeletal, Good Health and Well Being, aging, cell senescence, osteoarthritis, senolytics, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Chronic conditions associated with aging have proven difficult to prevent or treat. Senescence is a cell fate defined by loss of proliferative capacity and the development of a pro-inflammatory senescence-associated secretory phenotype comprised of cytokines/chemokines, proteases, and other factors that promotes age-related diseases. Specifically, an increase in senescent peripheral blood mononuclear cells (PBMCs), including T cells, is associated with conditions like frailty, rheumatoid arthritis, and bone loss. However, it is unknown if the percentage of senescent PBMCs associated with age-associated orthopedic decline could be used for potential diagnostic or prognostic use in orthopedics. Here, we report senescent cell detection using the fluorescent compound C12FDG to quantify PBMCs senescence across a large cohort of healthy and osteoarthritic patients. There is an increase in the percent of circulating C12FDG+ PBMCs that is commensurate with increases in age and senescence-related serum biomarkers. Interestingly, C12FDG+ PBMCs and T cells also were found to be elevated in patients with mild to moderate osteoarthritis, a progressive joint disease that is strongly associated with inflammation. The percent of C12FDG+ PBMCs and age-related serum biomarkers were decreased in a small subgroup of study participants taking the senolytic drug fisetin. These results demonstrate quantifiable measurements in a large group of participants that could create a composite score of healthy aging sensitive enough to detect changes following senolytic therapy and may predict age-related orthopedic decline. Detection of peripheral senescence in PBMCs and subsets using C12FDG may be clinically useful for quantifying cellular senescence and determining how and if it plays a pathological role in osteoarthritic progression.

Published
2024

9. Author Correction: Partial inhibition of mitochondrial complex I ameliorates Alzheimer’s disease pathology and cognition in APP/PS1 female mice

Author

Stojakovic, Andrea, Trushin, Sergey, Sheu, Anthony, Khalili, Layla, Chang, Su-Youne, Li, Xing, Christensen, Trace, Salisbury, Jeffrey L., Geroux, Rachel E., Gateno, Benjamin, Flannery, Padraig J., Dehankar, Mrunal, Funk, Cory C., Wilkins, Jordan, Stepanova, Anna, O’Hagan, Tara, Galkin, Alexander, Nesbitt, Jarred, Zhu, Xiujuan, Tripathi, Utkarsh, Macura, Slobodan, Tchkonia, Tamar, Pirtskhalava, Tamar, Kirkland, James L., Kudgus, Rachel A., Schoon, Renee A., Reid, Joel M., Yamazaki, Yu, Kanekiyo, Takahisa, Zhang, Song, Nemutlu, Emirhan, Dzeja, Petras, Jaspersen, Adam, Kwon, Ye In Christopher, Lee, Michael K., and Trushina, Eugenia

Published
2024
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13. The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2

Author

Chaib, Selim, López-Domínguez, José Alberto, Lalinde-Gutiérrez, Marta, Prats, Neus, Marin, Ines, Boix, Olga, García-Garijo, Andrea, Meyer, Kathleen, Muñoz, María Isabel, Aguilera, Mònica, Mateo, Lidia, Stephan-Otto Attolini, Camille, Llanos, Susana, Pérez-Ramos, Sandra, Escorihuela, Marta, Al-Shahrour, Fatima, Cash, Timothy P., Tchkonia, Tamara, Kirkland, James L., Abad, María, Gros, Alena, Arribas, Joaquín, and Serrano, Manuel

Published
2024
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14. Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used

Author

Harrison, David E., Strong, Randy, Reifsnyder, Peter, Rosenthal, Nadia, Korstanje, Ron, Fernandez, Elizabeth, Flurkey, Kevin, Ginsburg, Brett C., Murrell, Meredith D., Javors, Martin A., Lopez-Cruzan, Marisa, Nelson, James F., Willcox, Bradley J., Allsopp, Richard, Watumull, David M., Watumull, David G., Cortopassi, Gino, Kirkland, James L., Tchkonia, Tamar, Choi, Young Geun, Yousefzadeh, Matthew J., Robbins, Paul D., Mitchell, James R., Acar, Murat, Sarnoski, Ethan A., Bene, Michael R., Salmon, Adam, Kumar, Navasuja, and Miller, Richard A.

Published
2024
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17. Guidelines for minimal information on cellular senescence experimentation in vivo

Author

Ogrodnik, Mikolaj, Carlos Acosta, Juan, Adams, Peter D., d’Adda di Fagagna, Fabrizio, Baker, Darren J., Bishop, Cleo L., Chandra, Tamir, Collado, Manuel, Gil, Jesus, Gorgoulis, Vassilis, Gruber, Florian, Hara, Eiji, Jansen-Dürr, Pidder, Jurk, Diana, Khosla, Sundeep, Kirkland, James L., Krizhanovsky, Valery, Minamino, Tohru, Niedernhofer, Laura J., Passos, João F., Ring, Nadja A.R., Redl, Heinz, Robbins, Paul D., Rodier, Francis, Scharffetter-Kochanek, Karin, Sedivy, John M., Sikora, Ewa, Witwer, Kenneth, von Zglinicki, Thomas, Yun, Maximina H., Grillari, Johannes, and Demaria, Marco

Published
2024
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18. Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function

Author

Wang, Binsheng, Wang, Lichao, Gasek, Nathan S., Kuo, Chia-Ling, Nie, Jia, Kim, Taewan, Yan, Pengyi, Zhu, Junyu, Torrance, Blake L., Zhou, Yueying, Flores, Lisa C., Allen, Colton, Andrade, Allison M., Guo, Chun, Cohn, Rachel L., Jellison, Evan R., Bartley, Jenna M., Kuchel, George A., Li, Sheng, Pirtskhalava, Tamar, Tchkonia, Tamar, Yadav, Sumit, Haynes, Laura, Kirkland, James L., Ikeno, Yuji, and Xu, Ming

Published
2024
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19. Senolytic therapy in mild Alzheimer’s disease: a phase 1 feasibility trial

Author

Gonzales, Mitzi M., Garbarino, Valentina R., Kautz, Tiffany F., Palavicini, Juan Pablo, Lopez-Cruzan, Marisa, Dehkordi, Shiva Kazempour, Mathews, Julia J., Zare, Habil, Xu, Peng, Zhang, Bin, Franklin, Crystal, Habes, Mohamad, Craft, Suzanne, Petersen, Ronald C., Tchkonia, Tamara, Kirkland, James L., Salardini, Arash, Seshadri, Sudha, Musi, Nicolas, and Orr, Miranda E.

Published
2023
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20. Meeting Report: Aging Research and Drug Discovery

Author

Meron, Esther, Thaysen, Maria, Angeli, Suzanne, Antebi, Adam, Barzilai, Nir, Baur, Joseph A, Bekker-Jensen, Simon, Birkisdottir, Maria, Bischof, Evelyne, Bruening, Jens, Brunet, Anne, Buchwalter, Abigail, Cabreiro, Filipe, Cai, Shiqing, Chen, Brian H, Ermolaeva, Maria, Ewald, Collin Y, Ferrucci, Luigi, Florian, Maria Carolina, Fortney, Kristen, Freund, Adam, Georgievskaya, Anastasia, Gladyshev, Vadim N, Glass, David, Golato, Tyler, Gorbunova, Vera, Hoejimakers, Jan, Houtkooper, Riekelt H, Jager, Sibylle, Jaksch, Frank, Janssens, Georges, Jensen, Martin Borch, Kaeberlein, Matt, Karsenty, Gerard, de Keizer, Peter, Kennedy, Brian, Kirkland, James L, Kjaer, Michael, Kroemer, Guido, Lee, Kai-Fu, Lemaitre, Jean-Marc, Liaskos, David, Longo, Valter D, Lu, Yu-Xuan, MacArthur, Michael R, Maier, Andrea B, Manakanatas, Christina, Mitchell, Sarah J, Moskalev, Alexey, Niedernhofer, Laura, Ozerov, Ivan, Partridge, Linda, Passegué, Emmanuelle, Petr, Michael A, Peyer, James, Radenkovic, Dina, Rando, Thomas A, Rattan, Suresh, Riedel, Christian G, Rudolph, Lenhard, Ai, Ruixue, Serrano, Manuel, Schumacher, Björn, Sinclair, David A, Smith, Ryan, Suh, Yousin, Taub, Pam, Trapp, Alexandre, Trendelenburg, Anne-Ulrike, Valenzano, Dario Riccardo, Verburgh, Kris, Verdin, Eric, Vijg, Jan, Westendorp, Rudi GJ, Zonari, Alessandra, Bakula, Daniela, Zhavoronkov, Alex, and Scheibye-Knudsen, Morten

Subjects
Aging, aging, drug discovery, conference, AI, longevity, Biochemistry and Cell Biology, Physiology, Oncology and Carcinogenesis, Developmental Biology
Abstract

Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery (ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community.

Published
2022

21. The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice

Author

Xu, Qixia, Fu, Qiang, Li, Zi, Liu, Hanxin, Wang, Ying, Lin, Xu, He, Ruikun, Zhang, Xuguang, Ju, Zhenyu, Campisi, Judith, Kirkland, James L, and Sun, Yu

Subjects
Prevention, Complementary and Integrative Health, Aging, Nutrition, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Cancer, Animals, Apoptosis, Cell Line, Cellular Senescence, Computational Biology, Drug Development, Energy Metabolism, Flavonoids, Gene Expression Profiling, Gene Expression Regulation, Humans, Longevity, Mice, Mitochondria, Oxidative Stress, Senescence-Associated Secretory Phenotype, Senotherapeutics
Abstract

Ageing-associated functional decline of organs and increased risk for age-related chronic pathologies is driven in part by the accumulation of senescent cells, which develop the senescence-associated secretory phenotype (SASP). Here we show that procyanidin C1 (PCC1), a polyphenolic component of grape seed extract (GSE), increases the healthspan and lifespan of mice through its action on senescent cells. By screening a library of natural products, we find that GSE, and PCC1 as one of its active components, have specific effects on senescent cells. At low concentrations, PCC1 appears to inhibit SASP formation, whereas it selectively kills senescent cells at higher concentrations, possibly by promoting production of reactive oxygen species and mitochondrial dysfunction. In rodent models, PCC1 depletes senescent cells in a treatment-damaged tumour microenvironment and enhances therapeutic efficacy when co-administered with chemotherapy. Intermittent administration of PCC1 to either irradiated, senescent cell-implanted or naturally aged old mice alleviates physical dysfunction and prolongs survival. We identify PCC1 as a natural senotherapeutic agent with in vivo activity and high potential for further development as a clinical intervention to delay, alleviate or prevent age-related pathologies.

Published
2021

22. Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy.

Author

Prasanna, Pataje G, Citrin, Deborah E, Hildesheim, Jeffrey, Ahmed, Mansoor M, Venkatachalam, Sundar, Riscuta, Gabriela, Xi, Dan, Zheng, Guangrong, Deursen, Jan van, Goronzy, Jorg, Kron, Stephen J, Anscher, Mitchell S, Sharpless, Norman E, Campisi, Judith, Brown, Stephen L, Niedernhofer, Laura J, O'Loghlen, Ana, Georgakilas, Alexandros G, Paris, Francois, Gius, David, Gewirtz, David A, Schmitt, Clemens A, Abazeed, Mohamed E, Kirkland, James L, Richmond, Ann, Romesser, Paul B, Lowe, Scott W, Gil, Jesus, Mendonca, Marc S, Burma, Sandeep, Zhou, Daohong, and Coleman, C Norman

Subjects
Cancer, Prevention, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

Cellular senescence is an essential tumor suppressive mechanism that prevents the propagation of oncogenically activated, genetically unstable, and/or damaged cells. Induction of tumor cell senescence is also one of the underlying mechanisms by which cancer therapies exert antitumor activity. However, an increasing body of evidence from preclinical studies demonstrates that radiation and chemotherapy cause accumulation of senescent cells (SnCs) both in tumor and normal tissue. SnCs in tumors can, paradoxically, promote tumor relapse, metastasis, and resistance to therapy, in part, through expression of the senescence-associated secretory phenotype. In addition, SnCs in normal tissue can contribute to certain radiation- and chemotherapy-induced side effects. Because of its multiple roles, cellular senescence could serve as an important target in the fight against cancer. This commentary provides a summary of the discussion at the National Cancer Institute Workshop on Radiation, Senescence, and Cancer (August 10-11, 2020, National Cancer Institute, Bethesda, MD) regarding the current status of senescence research, heterogeneity of therapy-induced senescence, current status of senotherapeutics and molecular biomarkers, a concept of "one-two punch" cancer therapy (consisting of therapeutics to induce tumor cell senescence followed by selective clearance of SnCs), and its integration with personalized adaptive tumor therapy. It also identifies key knowledge gaps and outlines future directions in this emerging field to improve treatment outcomes for cancer patients.

Published
2021

23. Therapy-Induced Senescence: Opportunities to Improve Anti-Cancer Therapy

Author

Prasanna, Pataje G, Citrin, Deborah E, Hildesheim, Jeffrey, Ahmed, Mansoor M, Venkatachalam, Sundar, Riscuta, Gabriela, Xi, Dan, Zheng, Guangrong, van Deursen, Jan, Goronzy, Jorg, Kron, Stephen J, Anscher, Mitchell S, Sharpless, Norman E, Campisi, Judith, Brown, Stephen L, Niedernhofer, Laura J, O'Loghlen, Ana, Georgakilas, Alexandros G, Paris, Francois, Gius, David, Gewirtz, David A, Schmitt, Clemens A, Abazeed, Mohamed E, Kirkland, James L, Richmond, Ann, Romesser, Paul B, Lowe, Scott W, Gil, Jesus, Mendonca, Marc S, Burma, Sandeep, Zhou, Daohong, and Coleman, C Norman

Subjects
Cancer, Prevention, Good Health and Well Being, Biomarkers, Cellular Senescence, Humans, Neoplasms, Senescence-Associated Secretory Phenotype, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Cellular senescence is an essential tumor suppressive mechanism that prevents the propagation of oncogenically activated, genetically unstable, and/or damaged cells. Induction of tumor cell senescence is also one of the underlying mechanisms by which cancer therapies exert antitumor activity. However, an increasing body of evidence from preclinical studies demonstrates that radiation and chemotherapy cause accumulation of senescent cells (SnCs) both in tumor and normal tissue. SnCs in tumors can, paradoxically, promote tumor relapse, metastasis, and resistance to therapy, in part, through expression of the senescence-associated secretory phenotype. In addition, SnCs in normal tissue can contribute to certain radiation- and chemotherapy-induced side effects. Because of its multiple roles, cellular senescence could serve as an important target in the fight against cancer. This commentary provides a summary of the discussion at the National Cancer Institute Workshop on Radiation, Senescence, and Cancer (August 10-11, 2020, National Cancer Institute, Bethesda, MD) regarding the current status of senescence research, heterogeneity of therapy-induced senescence, current status of senotherapeutics and molecular biomarkers, a concept of "one-two punch" cancer therapy (consisting of therapeutics to induce tumor cell senescence followed by selective clearance of SnCs), and its integration with personalized adaptive tumor therapy. It also identifies key knowledge gaps and outlines future directions in this emerging field to improve treatment outcomes for cancer patients.

Published
2021

24. Transplanting old organs promotes senescence in young recipients

Author

Iske, Jasper, Roesel, Maximilian J., Martin, Friederike, Schroeter, Andreas, Matsunaga, Tomohisa, Maenosono, Ryoichi, Tripathi, Utkarsh, Xiao, Yao, Nian, Yeqi, Caldarone, Barbara J., Vondran, Florian W.R., Sage, Peter T., Azuma, Haruhito, Abdi, Reza, Elkhal, Abdallah, Pirtskhalava, Tamar, Tchkonia, Tamara, Kirkland, James L., Zhou, Hao, and Tullius, Stefan G.

Published
2024
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26. An untapped window of opportunity for glioma: targeting therapy-induced senescence prior to recurrence

Author

Riviere-Cazaux, Cecile, Carlstrom, Lucas P., Neth, Bryan J., Olson, Ian E., Rajani, Karishma, Rahman, Masum, Ikram, Samar, Mansour, Moustafa A., Mukherjee, Bipasha, Warrington, Arthur E., Short, Susan C., von Zglinicki, Thomas, Brown, Desmond A., Burma, Sandeep, Tchkonia, Tamar, Schafer, Marissa J., Baker, Darren J., Kizilbash, Sani H., Kirkland, James L., and Burns, Terry C.

Published
2023
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27. Challenges in developing Geroscience trials

Author

Rolland, Yves, Sierra, Felipe, Ferrucci, Luigi, Barzilai, Nir, De Cabo, Rafael, Mannick, Joan, Oliva, Anthony, Evans, William, Angioni, Davide, De Souto Barreto, Philipe, Raffin, Jeremy, Vellas, Bruno, and Kirkland, James L.

Published
2023
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31. Obesity, Senescence, and Senolytics

Author

Chaib, Selim, Tchkonia, Tamara, Kirkland, James L., Barrett, James E., Editor-in-Chief, Flockerzi, Veit, Editorial Board Member, Frohman, Michael A., Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Kuner, Rohini, Editorial Board Member, Michel, Martin C., Editorial Board Member, Page, Clive P., Editorial Board Member, Wang, KeWei, Editorial Board Member, Eckel, Juergen, editor, and Clément, Karine, editor

Published
2022
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34. List of contributors

Author

Abrantes, Margarida, primary, Alves, Raquel, additional, Anugula, Sharath, additional, Aran, Veronica, additional, Badimon, Lina, additional, Barreto, Jorge N., additional, Bartosz, Grzegorz, additional, Borges, Fernanda, additional, Borrás, Consuelo, additional, Botelho, Maria Filomena, additional, Bousquet, Jean, additional, Brehm, António M.D., additional, Brito, Gerly A.C., additional, Bultje, Daan, additional, Cabral, Ana Cristina, additional, Caetano, André, additional, Canhão, Helena, additional, Carreira, Isabel Marques, additional, Carriazo, Ana Maria, additional, Carvalho, Cristina, additional, Carvalho, Eugenia, additional, Castel-Branco, Margarida, additional, Chen, Yaohua, additional, Coelho-Filho, João M., additional, Constâncio, Vera, additional, Correia e Silva, António, additional, Costa, Deiziane V.S., additional, Costa, Elísio, additional, Costa, Inês, additional, Cunha-Oliveira, Teresa, additional, de Carvalho, Paulo, additional, De Luca, Vicenzo, additional, de Natale, Edoardo R., additional, Dias, Jorge, additional, Dias, Ronaldo P., additional, Duarte, Ana I., additional, Farrel, John, additional, Fernandez-Llimos, Fernando, additional, Ferreira, Lino, additional, Ferrucci, Luigi, additional, Figueiredo, Isabel Vitoria, additional, Ford, Jamie K., additional, Franceschi, Claudio, additional, Freitas, Alex A., additional, Furlan de Brito, Maja, additional, Giacomin, Karla C., additional, Girao, Henrique, additional, Gkikas, Ilias, additional, Gomes, Bárbara, additional, Gomes, Rodrigo M., additional, Gonçalves, Ana Cristina, additional, Goulden, Peter, additional, Grant, Marcus, additional, Grilo, Luís F., additional, Guldemond, Nick, additional, Henriques, Jorge, additional, Heringer, Manoela, additional, Illario, Maddalena, additional, Jerónimo, Carmen, additional, Jones, John G., additional, Jorge, Joana, additional, Kabiri, Yaschar, additional, Karkucinska-Wieckowska, Agnieszka, additional, Kelly, George, additional, Kirkland, James L., additional, Kitaeva, Kristina, additional, Kiyasov, Andrey, additional, Korolchuk, Viktor I., additional, Laranjo, Mafalda, additional, LaRocca, Thomas J., additional, Lavrador, Marta, additional, Lebiedzinska-Arciszewska, Magdalena, additional, Li, Zhiquan, additional, Liu, Yuezhong, additional, Lourenço, Alexandre, additional, Ma, Lina, additional, Malva, João O., additional, Martens, Christopher R., additional, Mas-Bargues, Cristina, additional, Matafome, Paulo, additional, Melo, Joana Barbosa, additional, Mendonça, Maria L. Lima, additional, Metaxakis, Athanasios, additional, Middleton, Lefkos T., additional, Moreira, Paula I., additional, Nascimento, Judite M., additional, Neto, Vivaldo M., additional, Oliveira, Paulo J., additional, Ori, Alessandro, additional, Oriá, Reinaldo B., additional, Ozanne, Susan E., additional, Padeiro, Miguel, additional, Padro, Teresa, additional, Palmeira, Carlos M., additional, Pan, Yiming, additional, Paredes, Simão, additional, Passos, João F., additional, Pereira, Edith, additional, Pereira, Francisco B., additional, Pereira, Susana P., additional, Pinton, Paolo, additional, Pires, Joana F., additional, Pires, Salomé, additional, Polidori, M. Cristina, additional, Politis, Marios, additional, Raimundo, Nuno, additional, Ramalho-Santos, João, additional, Rasmussen, Lene Juel, additional, Regateiro, Fernando J., additional, Reis, Dario D., additional, Ribeiro, Caio, additional, Ribeiro, Ilda Patrícia, additional, Ribeiro-Rodrigues, Teresa M., additional, Rizvanov, Albert, additional, Rocha, Teresa, additional, Röhr, Susanne, additional, Rolo, Anabela P., additional, Román-Domínguez, Aurora, additional, Romero-Ortuno, Roman, additional, Rosa, Manuel Santos, additional, Rutland, Catrin, additional, Sadowska-Bartosz, Izabela, additional, Santana, Paula, additional, Santinha, Deolinda, additional, Santos, Marcos, additional, Sarmento Ribeiro, Ana Bela, additional, Semedo, Deisa S.R.C., additional, Sequeira, João, additional, Sierra, Felipe, additional, Silva, Maria Natalina L., additional, Solana, Rafael, additional, Solovyeva, Valeriya, additional, Spínola, Hélder, additional, Tavares, Renata S., additional, Tavernarakis, Nektarios, additional, Tchkonia, Tamar, additional, Theng, Yin-Leng, additional, Traver-Salcedo, Vicente, additional, Udeh-Momoh, Chi, additional, Verma, Rakhi, additional, Victorelli, Stella, additional, Vilaça, Andreia, additional, Vilahur, Gemma, additional, Viña, José, additional, von Zglinicki, Thomas, additional, Wahl, Devin, additional, Werle, Berenice Maria, additional, Wieckowski, Mariusz R., additional, Wilson, Heather, additional, Wissler Gerdes, Erin O., additional, Wozniak, Lucyna A., additional, Zavan, Barbara, additional, Zhu, Yi, additional, and Zischka, Hans, additional

Published
2023
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36. Targeting senescent cells alleviates obesity‐induced metabolic dysfunction

Author

Palmer, Allyson K, Xu, Ming, Zhu, Yi, Pirtskhalava, Tamar, Weivoda, Megan M, Hachfeld, Christine M, Prata, Larissa G, van Dijk, Theo H, Verkade, Esther, Casaclang‐Verzosa, Grace, Johnson, Kurt O, Cubro, Hajrunisa, Doornebal, Ewald J, Ogrodnik, Mikolaj, Jurk, Diana, Jensen, Michael D, Chini, Eduardo N, Miller, Jordan D, Matveyenko, Aleksey, Stout, Michael B, Schafer, Marissa J, White, Thomas A, Hickson, LaTonya J, Demaria, Marco, Garovic, Vesna, Grande, Joseph, Arriaga, Edgar A, Kuipers, Folkert, von Zglinicki, Thomas, LeBrasseur, Nathan K, Campisi, Judith, Tchkonia, Tamar, and Kirkland, James L

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Nutrition, Obesity, Diabetes, 2.1 Biological and endogenous factors, Metabolic and endocrine, Cardiovascular, Adipocytes, Adipogenesis, Adipose Tissue, Aging, Animals, Cell Death, Cell Line, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Dasatinib, Female, Ganciclovir, Glucose, Humans, Inflammation, Insulin Resistance, Macrophages, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Quercetin, adipogenesis, aging, cellular senescence, dasatinib, quercetin, senolytics, type 2 diabetes, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Adipose tissue inflammation and dysfunction are associated with obesity-related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug-inducible "suicide" genes driven by the p16Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra-abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity-related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity-related metabolic dysfunction and its complications.

Published
2019

40. Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Author

Casso-Chapa, Bernardo, Vazquez González, Norma Alicia, Le, Nhat-Tu, Palaskas, Nicolas L., Nead, Kevin T., Eutsey, Lydia P., Samanthapudi, Venkata S.K., Osborn, Abigail M., Lee, Jonghae, Mejia, Gilbert, Hoang, Oanh, Lin, Steven H., Deswal, Anita, Herrmann, Joerg, Wang, Guangyu, Kirkland, James L., Krishnan, Sunil, Wehrens, Xander H.T., Chini, Eduardo N., and Yusuf, Syed Wamique

Published
2025
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41. Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans

Author

Zhu, Yi, Prata, Larissa G.P. Langhi, Gerdes, Erin O. Wissler, Netto, Jair Machado Espindola, Pirtskhalava, Tamar, Giorgadze, Nino, Tripathi, Utkarsh, Inman, Christina L., Johnson, Kurt O., Xue, Ailing, Palmer, Allyson K., Chen, Tingjun, Schaefer, Kalli, Justice, Jamie N., Nambiar, Anoop M., Musi, Nicolas, Kritchevsky, Stephen B., Chen, Jun, Khosla, Sundeep, Jurk, Diana, Schafer, Marissa J., Tchkonia, Tamar, and Kirkland, James L.

Published
2022
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43. Targeting p21Cip1 highly expressing cells in adipose tissue alleviates insulin resistance in obesity

Author

Wang, Lichao, Wang, Binsheng, Gasek, Nathan S., Zhou, Yueying, Cohn, Rachel L., Martin, Dominique E., Zuo, Wulin, Flynn, William F., Guo, Chun, Jellison, Evan R., Kim, Taewan, Prata, Larissa G.P. Langhi, Palmer, Allyson K., Li, Ming, Inman, Christina L., Barber, Lauren S., Al-Naggar, Iman M.A., Zhou, Yanjiao, Du, Wenqiang, Kshitiz, Kuchel, George A., Meves, Alexander, Tchkonia, Tamar, Kirkland, James L., Robson, Paul, and Xu, Ming

Published
2022
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48. A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues

Author

Saul, Dominik, Kosinsky, Robyn Laura, Atkinson, Elizabeth J., Doolittle, Madison L., Zhang, Xu, LeBrasseur, Nathan K., Pignolo, Robert J., Robbins, Paul D., Niedernhofer, Laura J., Ikeno, Yuji, Jurk, Diana, Passos, João F., Hickson, LaTonya J., Xue, Ailing, Monroe, David G., Tchkonia, Tamara, Kirkland, James L., Farr, Joshua N., and Khosla, Sundeep

Published
2022
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49. Rejuvenation of the aged brain immune cell landscape in mice through p16-positive senescent cell clearance

Author

Zhang, Xu, Pearsall, Vesselina M., Carver, Chase M., Atkinson, Elizabeth J., Clarkson, Benjamin D. S., Grund, Ethan M., Baez-Faria, Michelle, Pavelko, Kevin D., Kachergus, Jennifer M., White, Thomas A., Johnson, Renee K., Malo, Courtney S., Gonzalez-Suarez, Alan M., Ayasoufi, Katayoun, Johnson, Kurt O., Tritz, Zachariah P., Fain, Cori E., Khadka, Roman H., Ogrodnik, Mikolaj, Jurk, Diana, Zhu, Yi, Tchkonia, Tamara, Revzin, Alexander, Kirkland, James L., Johnson, Aaron J., Howe, Charles L., Thompson, E. Aubrey, LeBrasseur, Nathan K., and Schafer, Marissa J.

Published
2022
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